Rs Morosco

Stability of Amlodipine Besylate in Two Liquid Dosage Forms

OBJECTIVE To determine the stability of amlodipine besylate in two liquid dosage forms under refrigeration and at room temperature. DESIGN Commercially available amlodipine tablets (Norvasc-Pfizer) were used to prepare two suspensions: one in extemporaneously prepared 1% methylcellulose in syrup (1:1), and another in equal volumes of commercially available OraPlus/OraSweet. Each suspension containing amlodipine 1 mg/mL was stored in 10 plastic prescription bottles; 5 were stored at 4 degrees C and 5 at 25 degrees C. Samples were collected immediately after preparation (day 0) and on days 7, 14, 28, 42, 56, 70, and 91. Amlodipine concentration was measured by stability-indicating HPLC method (n = 15). SETTING Research laboratory at Childrens Hospital. MAIN OUTCOME MEASURES Physical and chemical stability (> 90% of the initial concentration) of amlodipine in the two extemporaneously prepared suspensions during storage in plastic prescription bottles at 4 degrees C and 25 degrees C. RESULTS Observed mean concentrations exceeded 90% of the initial concentrations in both suspensions for 91 days at 4 degrees C and 56 days at 25 degrees C. No noticeable change in physical appearance or odor was observed; pH changed slightly in the methylcellulose-containing formulation stored at 25 degrees C. CONCLUSION Amlodipine was stable in two suspensions when stored in plastic prescription bottles for 91 days at 4 degrees C or 56 days at 25 degrees C. These formulations may be considered for pediatric or elderly patients who are unable to swallow tablets. The liquid dosage form would also permit accurate administration of amlodipine doses to infants and young children based on their body weight.

Development of two stable oral suspensions of levodopa-carbidopa for children with amblyopia.

PURPOSE To develop stable liquid dosage forms of levodopa-carbidopa for use in children with amblyopia. METHODS Levodopa (100 mg) and carbidopa (25 mg) tablets were used to prepare the suspensions at 5 and 1.25 mg/mL, respectively. For each suspension, five bottles were stored at 25 degrees C and five at 4 degrees C. Three samples were taken from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days (n=15). Levodopa-carbidopa concentrations for each sample were measured in duplicate by validated and stability-indicating high-performance liquid chromatographic method. RESULTS The mean concentrations of levodopa-carbidopa in Ora Plus/Ora Sweet suspensions were 96% and 92% of the initial concentrations for 28 days at 25 degrees C, and 94% and 93% for 42 days at 4 degrees C. In the suspension containing ascorbic acid, the mean concentrations of levodopa-carbidopa were above 93% and 92% for 14 days at 25 degrees C, and 93% and 92% for 28 days at 4 degrees C. This liquid formulation was administered to 15 children (mean age: 5.6+/-1.4 years) with amblyopia. The number and type of adverse effects were similar in the levo-dopa-carbidopa versus placebo group. CONCLUSION Levodopa-carbidopa in extemporaneous suspensions prepared in Ora Plus and Ora Sweet were stable for 28 days when stored at 25 degrees C and for 42 days at 4 degrees C. Our data suggest our liquid formulation may be used safely in children with amblyopia.

Stability of Spironolactone in an Extemporaneously Prepared Suspension at Two Temperatures

OBJECTIVE: To determine the stability of spironolactone in an extemporaneously prepared suspension at 22 and 4°C over a three-month storage period. DESIGN: Spironolactone suspension (1 mg/mL) was prepared in syrup NF, carboxymethylcellulose, and purified water USP. The suspension was stored in ten amber glass prescription bottles; five were stored at 22°C and five at 4°C. Samples were drawn from each bottle and analyzed in duplicate (n=10) on days 0, 7, 14, 28, 42, 56, 70, and 91. Spironolactone concentrations were measured by a reproducible and stability-indicating HPLC method. Inspection of visual and pH changes also was performed on each study day. RESULTS: The mean concentration of spironolactone was always higher than 98 percent of its initial concentration. The pH and appearance of the suspension did not change substantially. CONCLUSIONS: Spironolactone was stable in a suspension containing syrup, carboxymethylcellulose, and purified water for three months during storage in amber glass bottles at both 22 and 4°C.

Effect of Preparation Method and Storage on Rifampin Concentration in Suspensions

OBJECTIVE: To determine the effect of four preparation methods and extended storage on rifampin concentration in extemporaneously prepared suspensions. DESIGN: Four preparation methods were used: mixing intravenous (iv) rifampin in syrup (A); manufacturers recommended technique of mixing capsule (Rifadin) contents in syrup (B); triturating capsule contents in syrup into a paste and adding remaining syrup while mixing (C); and triturating capsule contents in syrup into a paste, adding syrup, retriturating the slurry, and adding remaining syrup while mixing (D). Samples were drawn from each of five bottles of each of the four preparations stored at 4 °C, immediately after mixing (day 0), and on days 7, 14, 28, 42, 56, 70, and 91 days during storage. Rifampin wes measured by a stability-indicating HPLC method. RESULTS: The measured mean concentrations of rifampin were nearly 100 percent of the initial concentration in the suspension prepared from iv rifampin solution (method A) during the first 56 days of storage. In contrast, the measured concentrations were substantially lower than expected in the suspensions prepared by methods B, C, and D. The mean rifampin concentrations in suspensions prepared by methods B, C, and D were only 14.5, 38.6, and 68 percent, respectively, of the initial concentration achieved by method A. The rifampin concentrations increased with storage time in suspensions prepared by methods B, C, and D. The mean rifampin concentration was lower than 90 percent during the first 14 days with methods B and C, and the first 7 days with method D. The highest mean concentrations were observed on day 42 with method B, and on day 28 with methods C and D. All methods yielded 90% of the labeled potency (10 mg/mL) on day 56. CONCLUSIONS: Our results showed that preparation method can influence the dispersion, and thus the measured concentration, of rifampin in aliquots of suspensions prepared from capsules and stored in plastic bottles. Suspensions prepared from capsules led to lower-than-expected rifampin concentrations; those prepared from iv rifampin did not. Rifampin was stable in each type of suspension for 56 days at 4 °C.

Measurement of Ceftazidime Arginine in Aqueous Solution by HPLC

Abstract Ceftazidime is used widely for the treatment of infections caused by gram-negative microorganisms. Ceftazidime arginine is its newest formulation available in the U.S. It is reconstituted and stored in plastic syringes. A high-performance liquid chromatographic (HPLC) method was developed to measure ceftazidime arginine in aqueous solution to determine its stability during storage in plastic syringes. The chromatographic separation was achieved using an ultrasphere ODS column and mobile phase containing 89% 0.01M ammonium acetate buffer and 11% methanol, at a detection wave length of 254 nm. The retention time of ceftazidime arginine was about 4.27 minutes. The accuracy ranged from 98.6 to 99.8% and the coefficient of variation was less than 1%. The technique was used to determine the stability of ceftazidime arginine in sterile water for injection during storage for 24 hours in plastic syringes.

Stability of rifampin in two suspensions at room temperature.

The objective of our study was to determine the stability of rifampin (rifampicin) in two extemporaneously prepared suspensions at room temperature. Two suspensions were prepared in syrup by using intravenous rifampin (A) or rifampin capsules (B). Each suspension was stored in five plastic prescription bottles. During the first week, the mean measured concentrations of rifampin were nearly 100% of initial concentration in suspension A, but were 77–83% of the expected (labelled) concentration in suspension B. The maximum concentrations of rifampin were observed immediately after preparation of suspension A, but not until 14 days in suspension B. On day 56, the mean concentration of rifampin was about 95% of initial concentration in suspension A, and close to 90% of the labelled potency (10 mg/ml) in suspension B. Rifampin was found to be chemically stable in each suspension for 56 days at room temperature. Suspensions prepared from the capsules may be non‐homogeneous and lead to unsatisfactory dosing.

Stability and compatibility of anakinra with ceftriaxone sodium injection in 0·9% sodium chloride or 5% dextrose injection

The stability and compatibility of anakinra (recombinant human interleukin‐1 receptor antagonist) with ceftriaxone sodium in 0·9% sodium chloride or 5% dextrose injection was determined during a 4‐h period at ambient room temperature and light. Anakinra was diluted in 0·9% sodium chloride or 5% dextrose to the concentrations of 4 and 36 mg/ml. Anakinra, at each concentration was mixed with ceftriaxone sodium (20 mg/ml) in a 50 : 50 proportion and stored in plastic culture vials with polypropylene caps. The samples were collected at 0, 2 and 4 h after mixing. Anakinra and ceftriaxone concentrations were measured using stability‐indicating HPLC methods.

Stability and compatibility of anakinra with intravenous cimetidine hydrochloride or famotidine in 0.9% sodium chloride injection

We designed a study to evaluate the stability and compatibility of anakinra (recombinant human interleukin–1 receptor antagonist) with cimetidine hydrochloride or famotidine in 0–9% sodium chloride injection during a 4–h period at room temperature (22°C) and light. Anakinra was diluted in 0–9% sodium chloride to concentrations of 4 and 36 mg/ml. At each concentration, anakinra was mixed with 3 mg/ml cimetidine or with 1 mg/ml famotidine, in a 50:50 proportion and stored in plastic culture vials with polypropylene caps.

Extended stability of iobenguane under simulated clinical conditions

PURPOSE The stability of iobenguane sulfate stored at 4-7 degrees C over 91 days was studied. METHODS An iobenguane sulfate solution at a concentration of 2.2 mg/mL was prepared in a top-fill i.v. bag using 143 mg of iobenguane sulfate and 65 mL of Sterile Water for Injection, USP. The solution was poured through a 0.22- microm filter assembly for sterilization into 60 1-mL polycarbonate plastic syringes. Each syringe was filled with 0.9 mL of the iobenguane sulfate solution and stored in amber plastic bags at 4-7 degrees C. The stability of iobenguane sulfate was analyzed using high-performance liquid chromatography immediately after solution preparation and on days 7, 14, 28, 42, 56, 70, and 91. Samples were inspected for chemical purity by observing for particulate formation and color change. RESULTS The mean concentration of ioben-guane exceeded 93% of the initial concentration in all samples throughout the 91-day study period. No changes in color or turbidity were observed. CONCLUSION Iobenguane sulfate 2.2 mg/mL was stable for 91 days when stored in polycarbonate syringes at 4-7 degrees C.